About CRISPR Cas-9

• CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. 

• The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays.
• The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.

• This also contains Cas (CRISPR-associated) genes that are used to produce enzymes such as Cas-9. These enzymes — the Cas-9 being a particularly popular one — can be used to chop the DNA of the virus and destroy them.
• The CRISPR-Cas9 system works similarly in the lab. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location.
• Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

How can this be used to edit genomes?

• Using the tool, researchers can change the DNA of animals, plants and microorganisms with precision. 
• Emmanuelle Charpentier, who is now director, Max Planck Institute for Infection Biology, Berlin, had studied Streptococcus pyogenes, a species of bacteria known to be associated with a range of illnesses such as pharyngitis, tonsillitis and scarlet fever. 
• While studying this, she discovered a previously unknown molecule, tracrRNA. 
• Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.
• Dr. Charpentier published her discovery in 2011. The same year, she initiated a collaboration with biochemist Jennifer Doudna, now a professor at the University of California, Berkeley.
• Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.
• In a significant experiment, they reprogrammed the genetic scissors.
• In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. 
• Where the DNA is cut it is then easy to rewrite the code of life.

How is the tool different from other editing systems?

• Other genome editing systems like TALENs and Zinc-Finger Nucleases can do similar jobs, but several users consider the Charpentier-Doudna tool more adaptable and easier to use.

• Coupled with the availability of genome sequences for a growing number of organisms, the technology allows researchers to find out what genes do, move mutations that are identified and associated with disease into systems where they can be studied and tested for treatment, or where they can be tested in combinations with other mutations.

To what uses has CRISPR/Cas9 been deployed so far?

• Hereditary blindness
• Beta thalassemia 
• Sickle cell disease 
• Research is already underway for using proteins that are smaller and more efficient than Cas-9, though the system purportedly holds promise for treating more complex diseases, such as cancer, heart diseases, mental illnesses, and the human immunodeficiency virus (HIV) infection.

Drawbacks of CRISPR

Even though the CRISPR/Cas-9 system allows a democratic usage in labs across the world to tinker with genomes, it still has not reached the level of precision required to be sure that it does not cause unintentional side effects.

Reference:

https://www.thehindu.com/sci-tech/science/the-hindu-explains-how-does-a-genome-editing-tool-developed-by-two-women-scientists-help-in-tackling-diseases/article32823954.ece